RB_A

Retinoblastoma-like and retinoblastoma-associated proteins may have a function in cell cycle regulation. They form a complex with adenovirus E1A and Simian virus 40 (SV40) large T antigen, and may bind and modulate the function of certain cellular proteins with which T and E1A compete for pocket binding. The proteins may act as tumor suppressors, and are potent inhibitors of E2F-mediated trans-activation. This domain has the cyclin fold [(PUBMED:8152925)].

The crystal structure of the Rb pocket bound to a nine-residue E7 peptide containing the LxCxE motif, shared by other Rb-binding viral and cellular proteins, shows that the LxCxE peptide binds a highly conserved groove on the B-box portion of the pocket; the A-box portion appears to be required for the stable folding of the B box (see IPR002719). Also highly conserved is the extensive A-B interface, suggesting that it may be an additional protein-binding site. The A and B boxes each contain the cyclin-fold structural motif, with the LxCxE-binding site on the B-box cyclin fold being similar to a Cdk2-binding site of cyclin A and to a TBP-binding site of TFIIB [(PUBMED:9495340)].

The A and B boxes are found at the C-terminal end of the protein; the A-box is on N-terminal side of the B-box.

Structure of the retinoblastoma tumour-suppressor pocket domain bound to apeptide from HPV E7.

Nature. 1998; 391: 859-65

Display abstract

The pocket domain of the retinoblastoma (Rb) tumour suppressor is central to Rbfunction, and is frequently inactivated by the binding of the human papillomavirus E7 oncoprotein in cervical cancer. The crystal structure of the Rb pocketbound to a nine-residue E7 peptide containing the LxCxE motif, shared by otherRb-binding viral and cellular proteins, shows that the LxCxE peptide binds ahighly conserved groove on the B-box portion of the pocket; the A-box portionappears to be required for the stable folding of the B box. Also highly conservedis the extensive A-B interface, suggesting that it may be an additionalprotein-binding site. The A and B boxes each contain the cyclin-fold structuralmotif, with the LxCxE-binding site on the B-box cyclin fold being similar to aCdk2-binding site of cyclin A and to a TBP-binding site of TFIIB.